Medical journal of Hiroshima Universtiy Volume 50 Issue 3/4
2002-08-28 発行

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP)投与Donryuラットに誘発した拡張型心筋症 <原著>

Cardiomyopathy in 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Treated Donryu Rats
Ishimura, Yoshimasa
2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) is a heterocyclic amine derived from cooked meat and a potent environmental carcinogen for rat colon, prostate and mammary glands. PhIP (75 mg/kg/day) treatment by gavage ten times on alternate days caused increases in mortality and incidence of dilated cardiomyopathy in Crj : Donryu rats after the 52-week study period. Microscopically, vacuolization/necrosis of the cardiac muscle, inflammatory cell infiltration and fibrosis in the left ventricle, atrial thrombosis and left ventricular dilatation were observed in the heart from Week 4 of the study period. Electoronmicroscopically, decrease of myofibrils, increase of mitochondria and dilatation of sarcoplasmic reticulum were observed. PhIP (20,40 and 75 mg/kg/day) treatments decreased blood pressures temporarily in Week 4. PhIP-DNA adduct levels increased in Week 4 of PhIP (20,40 and 75 mg/kg/day) treatments and decreased in Week 13 of PhIP (75 mg/kg/day) treatment. These results suggest that the increases in mortality and incidences of dilated cardiomyopathy in Crj : Donryu rats by high dose of PhIP treatment were caused by the action of PhIP against the cardiac muscle, which may be related to PhIP-DNA adduct formation in the cardiac muscle cells.
Donryu rat
Dilated cardiomyopathy